Modulation of the c-Jun N-terminal kinase activity in the embryonic heart in response to anoxia-reoxygenation: involvement of the Ca2+ and mitoKATP channels.

Whether the response of the fetal heart to ischemia-reperfusion is associated with activation of the c-Jun N-terminal kinase (JNK) pathway is not known. In contrast, involvement of the sarcolemmal L-type Ca2+ channel (LCC) and the mitochondrial KATP (mitoKATP) channel has been established. This work aimed at investigating the profile of JNK activity during anoxia-reoxygenation and its modulation by LCC and mitoK(ATP) channel. Hearts isolated from 4-day-old chick embryos were submitted to anoxia (30 min) and reoxygenation (60 min). Using the kinase assay method, the profile of JNK activity in the ventricle was determined every 10 min throughout anoxia-reoxygenation. Effects on JNK activity of the LCC blocker verapamil (10 nM), the mitoK(ATP) channel opener diazoxide (50 microM) and the blocker 5-hydroxydecanoate (5-HD, 500 microM), the mitochondrial Ca2+ uniporter (MCU) inhibitor Ru360 (10 microM), and the antioxidant N-(2-mercaptopropionyl) glycine (MPG, 1 mM) were determined. In untreated hearts, JNK activity was increased by 40% during anoxia and peaked fivefold relative to basal level after 30-40 min reoxygenation. This peak value was reduced by half by diazoxide and was tripled by 5-HD. Furthermore, the 5-HD-mediated stimulation of JNK activity during reoxygenation was abolished by diazoxide, verapamil or Ru360. MPG had no effect on JNK activity, whatever the conditions. None of the tested pharmacological agents altered JNK activity under basal normoxic conditions. Thus, in the embryonic heart, JNK activity exhibits a characteristic pattern during anoxia and reoxygenation and the respective open-state of LCC, MCU and mitoKATP channel can be a major determinant of JNK activity in a ROS-independent manner.

The activation of the atypical PKC zeta in light-induced retinal degeneration and its involvement in L-DNase II control.

Light-induced retinal degeneration is characterized by photoreceptor cell death. Many studies showed that photoreceptor demise is caspase-independent. In our laboratory we showed that leucocyte elastase inhibitor/LEI-derived DNase II (LEI/L-DNase II), a caspase-independent apoptotic pathway, is responsible for photoreceptor death. In this work, we investigated the activation of a pro-survival kinase, the protein kinase C (PKC) zeta. We show that light exposure induced PKC zeta activation. PKC zeta interacts with LEI/L-DNase II and controls its DNase activity by impairing its nuclear translocation. These results highlight the role of PKC zeta in retinal physiology and show that this kinase can control caspase-independent pathways.

Quality time: exploring meaningful mandatory community involvement programs in secondary schools /

The purpose of this study was to explore the experiences of 5 stakeholder groups—students, parents, community organization representatives, guidance counsellors, and secondary school principals—in dealing with a mandatory secondary school graduation requirement in Ontario. The requirement is that students must complete 40 hours of eligible community involvement activities during their high school years in order to graduate. Ten stakeholders were interviewed regarding the nature of the community involvement program, what makes it work, and suggestions for improvement. The study found that although this program has the potential to provide a meaningful experience for students, and students are seen to gain from their experience in multiple ways, it depends substantially on the commitment of students, educators, and community organizations to make it worthwhile. Stakeholders recommended changes to the current program, which included making it a more structured process that would increase the consistency ofhow this program is implemented, finding ways to curb cheating and to reduce the administrative burden on schools, having more support from the Ontario provincial government and Ontario Ministry of Education and Training in the promotion and communication of this program, and developing partnerships between community organizations and schools to enrich the application of this program. This study concludes with a recommendation that the Ontario Ministry of Education and Training consider introducing Service-Learning, a curriculum-based experiential service and learning process, as an enhancement to the current community involvement program.

Co-operative education and the development of self-esteem, an internal locus of control and work habits

This study compared approximately 50 grade 12 students studying In th~ co-operative education mode with approximately 50 grade 12 students studying in a traditional English course. Measures of self-esteem, locus of control and work habits were compared before and at the conclusion of one semester's involvement in the different programs. Using Coopersmith's Self-Esteem Inventory, the students who had chosen to study in the co-operative education mode scored significantly higher than the students in the traditional course. At the end of the semester, the co-operative education students' scores remained significantly higher than the English students'. Although the test showed no sjgnifi~ant changes in self-esteem. anecdotal reports indicated that co-operative education students had increased self-esteem over the semester. No significant differences in locus of control were observed between the two groups at any time. Significant differences in work habits were observed. While both groups had the same number of absences and the same marks before taking these courses, students who were involved in co-operative education had significantly fewer absences and significantly higher marks than the students studying in the traditional course. Anecdotal reports also indicated an improv~ment in work habits for students who had been involved in co-operative education. Recommendations of the study are for further research to determine more exactly how self-esteem and work habits develop in co-operative education students. Also. students. parents, teachers. and administrators need to be made aware of the success of this program.

Adult perceptions of student involvement in schoolyard gardening /

The purpose of this research is to investigate through adult perceptions what factors have enabled and limited student participation in schoolyard gardening, and how to support student involvement in schoolyard gardening. It is a collective case study of three schools in the Toronto District School Board (TDSB, Ontario, Canada) that are currently running a schoolyard gardening project. Sixteen interviews were conducted during May and June, 2005, and photos of the three schoolyard gardens were taken. The results show that the common factors that have enabled student participation in schoolyard gardening at the three schools are teacher's initiative and commitment, principal's leadership and support, parental involvement and donations, and the TDSB's EcoSchools program and workshops. The common limiting factors are time, money, and the unions' "work-to-rule" issue. The ways to support student involvement include teachers integrating the gardening into the curriculum; parents making donations to the school and creating a family gardening culture; principals supporting in money or budget and taking the lead; the TDSB providing funding, awards, incentives, and more maintenance; and the Ontario Ministry of Education supplying funding, curriculum link, and teacher training.

Ethnic Minority Parents' Involvement in Education: Exploring and Understanding Their Experiences

Lopez, Scribner and Mahitivanichcha (2001) discuss the limited volume of literature that directly addresses ethnic minority parents' involvement in their children's education and they call upon researchers to fill this gap in the literature. This study is one such positive step with its focus on exploring how ethnic minority parents of secondary school students in southern Ontario understand their involvement in their children's education. Participants in the study included three ethnic minority parents recruited from a local adult education centre, and my parents who, as ethnics minority parents, also faced challenges trying to support their children as we progressed through the Ontario educational system. Primary data were collected through in-depth, open-ended interviews approximately one hour in length. Each of the five participants was interviewed twice. Secondary data included Ontario Ministry of Education documents that addressed programs, policies, and supports for ethnic minority students in Ontario secondary schools. Fieldnotes and a research journal also provided secondary data. The findings highlight, among other things, the challenges the participants faced as ethnic minority parents with a deep desire to support their children's education, but often lacking the cultural capital valued in the Ontario school system to meet that goal. As well, I benefited greatly from this research learning about the various ways in which, in my future work as a teacher of ethnic minority students, I can integrate the knowledge, skills, and experiences of ethnic minorities into my practice to ensure that parents of the non-dominant culture have an opportunity to become highly involved in the education of their children.

Aboriginal Parental Involvement/Engagement for Student Success

An increasing body of knowledge links parental involvement with student success but few studies address Aboriginal parental involvement in urban settings. While some critics argue traditional Aboriginal knowledge is best delivered at home, Aboriginal children who share parents’ stories in the classroom benefit other children who draw connections to these stories. Moreover, Aboriginal learners need to function in mainstream Western society and in public school settings in which educators often have a difficult time engaging Aboriginal parents. Consequently, this research sought to explore the perceptions and sense of engagement of parents/caregivers in the Aboriginal Student Program (ASP) in a publicly funded secondary school in Ontario. The study was an extension of the researcher’s existing work and focused specifically on a sample of parents/caregivers taking part in an Aboriginal feast at an Ontario secondary school. Nine individuals accepted an invitation to participate in a Talking Circle and shared perceptions of their children’s educational experiences. Data were collected and coded, and findings indicated that parental involvement in children’s educational journeys contributed significantly to a sense of parental engagement in the school and in Aboriginal programs. Results also suggest that Eurocentric pedagogy can be modified in mainstream secondary schools to directly involve Aboriginal parents/caregivers. Although many participants’ stories revealed they experienced racism during their own schooling, study findings demonstrate that the parents/caregivers want to be involved in their children’s education nonetheless. This thesis discusses the data that were grounded in the participants’ voices that in turn led to several key recommendations.

Patient and public involvement in healthcare quality improvement: how organizations can help patients and professionals to collaborate

Citizens across the world are increasingly called upon to participate in healthcare improvement. It is often unclear how this can be made to work in practice. This 4- year ethnography of a UK healthcare improvement initiative showed that patients used elements of organizational culture as resources to help them collaborate with healthcare professionals. The four elements were: (1) organizational emphasis on nonhierarchical, multidisciplinary collaboration; (2) organizational staff ability to model desired behaviours of recognition and respect; (3) commitment to rapid action, including quick translation of research into practice; and (4) the constant data collection and reflection process facilitated by improvement methods.

Time for review: supporting the work of an advisory group

This paper raises methodological issues about the challenges and dilemmas of inclusive research practices reflecting on the work of an advisory group carrying out research on using Information and Communication Technology (ICT) to enhance community participation. The interests of three parties can be identified – the commissioning agent, the researchers and the researched – and these interplayed throughout the course of the research determining the outcomes. Given the relationship between inclusive research and advocacy, there were particular gains in enabling the voice of the advisory group to shape the way in which the research was conducted and to disseminate the findings both within the organisation and beyond. However, the fragility of these new structures required organisational changes for the research to be truly empowering. The experience of the group suggests the need for their involvement at all stages of the research process

Crotoxin alters lymphocyte distribution in rats: Involvement of adhesion molecules and lipoxygenase-derived mediators

Crotoxin is the main neurotoxic component of Crotalus durissus terrificus snake venom and modulates immune and inflammatory responses, interfering with the activity of leukocytes. In the present work, the effects of crotoxin on the number of blood and lymphatic leukocytes and on lymph nodes and spleen lymphocytes population were investigated. The toxin s.c. administered to male Wistar rats, decreases the number of lymphocytes in blood and lymph circulation and increases the content of B and T-lymphocytes in lymph nodes. These effects were detected 1-2 h after treatment. The crotoxin molecule is composed of two subunits, an acidic non-toxic polypeptide, named crotapotin and a toxic basic phospholipase A(2) (PLA(2)). PLA(2), but not crotapotin, decreased the number of circulating blood and lymph lymphocytes. Crotoxin promotes leukocyte adherence to endothelial cells of blood microcirculation and to lymph node high endothelial venules, which might contribute to the drop in the number of circulating lymphocytes. Crotoxin increases expression of the adhesion molecule LFA-1 in lymphocytes. The changes in the expression of the adhesion molecule might contribute, at least in part, for the increased leukocyte adhesion to endothelium. Zileuton, a 5-lipoxygenase inhibitor, blocked the decrease in the number of circulating leukocytes induced by crotoxin and also abolished the changes observed in leukocyte-endothelial interactions, suggesting the involvement of lipoxygenase-derived mediators in the effects of the toxin. (c) 2008 Elsevier Ltd. All rights reserved.

Structural modeling and mutational analysis of yeast eukaryotic translation initiation factor 5A reveal new critical residues and reinforce its involvement in protein synthesis

Eukaryotic translation initiation factor 5A (eIF5A) is a protein that is highly conserved and essential for cell viability. This factor is the only protein known to contain the unique and essential amino acid residue hypusine. This work focused on the structural and functional characterization of Saccharomyces cerevisiae eIF5A. The tertiary structure of yeast eIF5A was modeled based on the structure of its Leishmania mexicana homologue and this model was used to predict the structural localization of new site-directed and randomly generated mutations. Most of the 40 new mutants exhibited phenotypes that resulted from eIF-5A protein-folding defects. Our data provided evidence that the C-terminal alpha-helix present in yeast eIF5A is an essential structural element, whereas the eIF5A N-terminal 10 amino acid extension not present in archaeal eIF5A homologs, is not. Moreover, the mutants containing substitutions at or in the vicinity of the hypusine modification site displayed nonviable or temperature-sensitive phenotypes and were defective in hypusine modification. Interestingly, two of the temperature-sensitive strains produced stable mutant eIF5A proteins - eIF5A(K56A) and eIF5A(Q22H,L93F)- and showed defects in protein synthesis at the restrictive temperature. Our data revealed important structural features of eIF5A that are required for its vital role in cell viability and underscored an essential function of eIF5A in the translation step of gene expression.

Co-stressors chilling and high light increase photooxidative stress in diuron-treated red alga Kappaphycus alvarezii but with lower involvement of H(2)O(2)

Diuron is one of the most commonly found N-phenylurea herbicides in marine/estuarine waters that promotes toxic effects by inhibiting photosynthesis and affecting the production of reactive oxygen species (ROS) in autotrophs. Since photo- and thermoacclimation are also ROS-mediated processes, this work evaluates a hypothetical additive effect of high light (HL) and chilling (12 degrees C) on 50 nM diuron toxicity to the highly-photosynthetically active apices of the red alga Kappaphycus alvarezii. Additive inhibition of photosynthesis was mainly evidenced by significant decreases of quantum yield of photosystem II and electron transfer rates upon co-stressors exposure to diuron-treated algae. Under extreme 12 degrees C/HL/diuron conditions, unexpected lower correlations between H(2)O(2) concentrations in seawater and radical-sensitive protein thiols were concomitantly measured with the highest indexes of photoinhibition (parameter beta). Altogether, these data support the hypothesis that co-stressors chilling/HL additively inhibit photosynthesis in diuron-exposed K. alvarezii but with less involvement of H(2)O(2) in injury effects than with only chilling or HL. (C) 2010 Elsevier Inc. All rights reserved.

Predicting and breaking sedentary behaviour at work

This thesis aimed at designing and developing a system that can a) infer individuals’ need for a break from sedentary behaviour in the workplace, and b) persuade them to take a break through the use of different techniques from persuasive psychology. We postulated three variables, namely, individuals’ posture, stress levels and involvement in their computer mediated activity. We developed and field-studied a system that could infer these using a web camera and a key presses and mouse clicks log. We found that the system could predict posture from viewing depth and stress from the movement detected. We then created a general formula that predicts individuals’ need for a break using only the posture and stress predictors. Once the first objective was set, we built and field-studied a system that used three ways to communicate a recommendation for a break to a user: implicit, just-in time and ambient feedback. The implicit feedback was operationalized through changes in the users’ computer wallpaper that provided subtle visual cues. The just-in time feedback employed prompting at the bottom right side of the user’s screen. In addition, we implemented an intuitive behind-screen interaction technique where people can snooze a notification using simple gestures. The ambient feedback mechanism employed an origami sculpture sitting on the user’s desk. This prototype was continuously reflecting the user’s posture and performed rhythmic movements when to recommend breaks. A field study demonstrated the overall success of the system, with 69% of the break recommendations received by users were accepted. The study further revealed the strengths and weaknesses of the three persuasive mechanisms.

Structural modeling and mutational analysis of yeast eukaryotic translation initiation factor 5A reveal new critical residues and reinforce its involvement in protein synthesis

Eukaryotic translation initiation factor 5A (eIF5A) is a protein that is highly conserved and essential for cell viability. This factor is the only protein known to contain the unique and essential amino acid residue hypusine. This work focused on the structural and functional characterization of Saccharomyces cerevisiae eIF5A. The tertiary structure of yeast eIF5A was modeled based on the structure of its Leishmania mexicana homologue and this model was used to predict the structural localization of new site-directed and randomly generated mutations. Most of the 40 new mutants exhibited phenotypes that resulted from eIF-5A protein-folding defects. Our data provided evidence that the C-terminal alpha-helix present in yeast eIF5A is an essential structural element, whereas the eIF5A N-terminal 10 amino acid extension not present in archaeal eIF5A homologs, is not. Moreover, the mutants containing substitutions at or in the vicinity of the hypusine modification site displayed nonviable or temperature-sensitive phenotypes and were defective in hypusine modification. Interestingly, two of the temperature-sensitive strains produced stable mutant eIF5A proteins - eIF5A(K56A) and eIF5A(Q22H,L93F)- and showed defects in protein synthesis at the restrictive temperature. Our data revealed important structural features of eIF5A that are required for its vital role in cell viability and underscored an essential function of eIF5A in the translation step of gene expression.

Periacinar Retraction Clefting in Nonneoplastic and Neoplastic Prostatic Glands: Artifact or Molecular Involvement

A space between neoplastic acini and prostatic stroma is not rare and studies have interpreted this as an artifact, considering the absence of endothelial cells indicating vascular invasion. Thus, the aims of this work were to characterize and correlate the occurrence and extent of retraction clefting with the reactivities of alpha and beta dystroglycan (alpha DG, beta DG), laminin, matrix metalloproteinase 2 (MMP-2), p63, insulin-like growth factor 1(IGF-1), vimentin, and fibroblast growth factor 2 (FGF-2). The study was based on nonneoplastic and neoplastic prostatic tissues obtained from necropsies and retropubic radical prostatectomies. The results showed that periacinar retraction clefting was significantly more frequent in prostatic carcinoma samples than in normal prostatic acini. Most of the neoplastic acini (72.0%) showed retraction clefting of more than 50% of circumference, which were significantly more frequent in Gleason score 7 and 6. Decreased collagen and reticular and elastic fibers were verified in the stroma around neoplastic acini. Weak and discontinuous alpha DG, beta DG, and laminin immunoreactivities and intensified MMP-2, vimentin, IGF-1 and FGF-2 immunoreactivities were verified in the neoplastic acini; p63 immunoreactivity was negative in all carcinomas. Thus, these findings showed that the lack of epithelial basal cells, DGs, and laminin and increased MMP-2, IGF-1, and FGF-7 could be considered important pathways in periacinar retraction occurrence. This study demonstrated the origin of and the biological mechanisms responsible for periacinar retraction clefting in prostatic carcinoma.